What is the mechanism of action and uses of Prucalopride (Serotonin 5-HT4 receptor agonist)?

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From the Guidelines

Prucalopride is a selective serotonin type 4 (5-HT4) receptor agonist that should be used as a primary treatment for chronic idiopathic constipation in adults, given its efficacy in improving bowel movements and quality of life, as demonstrated in recent clinical guidelines 1.

Mechanism of Action and Uses

Prucalopride's mechanism of action involves stimulating 5-HT4 receptors in the gastrointestinal tract, enhancing colonic motility by increasing acetylcholine release from enteric neurons, which promotes high-amplitude propagating contractions in the colon, accelerating transit time and facilitating bowel movements 1.

Dosage and Administration

The typical dosage is 2 mg once daily for adults, though elderly patients (over 65) and those with severe renal impairment should start with 1 mg daily, as recommended by recent clinical practice guidelines 1.

Side Effects and Safety Profile

Common side effects include headache, abdominal pain, nausea, and diarrhea, which often diminish after the first few days of treatment 1. Unlike other promotility agents, prucalopride has minimal interaction with hERG potassium channels, resulting in a better cardiovascular safety profile.

Clinical Benefits

It's particularly valuable for patients who haven't responded adequately to laxatives, with clinical studies showing it can increase spontaneous complete bowel movements and improve quality of life in chronic constipation patients 1.

Key Considerations

The medication typically begins working within the first week of treatment, though some patients may require several weeks to experience full benefits. Patients and clinicians should be alert to unusual changes in mood and behavior and suicidal ideation, although the causal association between prucalopride and risk of suicide is unclear 1. Prucalopride is contraindicated in patients with intestinal perforation or obstruction, Crohn’s disease, ulcerative colitis, and toxic megacolon/megarectum.

From the FDA Drug Label

Prucalopride, a selective serotonin type 4 (5-HT4) receptor agonist, is a gastrointestinal (GI) prokinetic agent that stimulates colonic peristalsis (high-amplitude propagating contractions [HAPCs]), which increases bowel motility Prucalopride tablet is a serotonin-4 (5-HT4) receptor agonist indicated for the treatment of chronic idiopathic constipation (CIC) in adults.

The mechanism of action of prucalopride is as a serotonin type 4 (5-HT4) receptor agonist, which stimulates colonic peristalsis and increases bowel motility. The uses of prucalopride include the treatment of chronic idiopathic constipation (CIC) in adults 2 2. Key points about prucalopride include:

  • It is a gastrointestinal prokinetic agent
  • It stimulates high-amplitude propagating contractions (HAPCs)
  • It increases bowel motility
  • It is indicated for the treatment of CIC in adults

From the Research

Mechanism of Action

  • Prucalopride is a selective 5-HT4 receptor agonist with colonic prokinetic activity 3, 4, 5, 6, 7
  • It directly stimulates colonic motility, differentiating it from other medications approved for chronic constipation 3

Uses

  • Prucalopride is indicated for the treatment of chronic idiopathic constipation in adults 3, 4, 5, 6, 7
  • It has also demonstrated promise in the treatment of gastroparesis, post-operative ileus, and opioid-induced constipation 3
  • Prucalopride may be used in patients with chronic constipation who have not experienced adequate relief with laxatives 4, 6

Efficacy

  • Prucalopride has been shown to improve bowel function, increase complete spontaneous bowel movements, and reduce constipation-related symptoms in patients with chronic idiopathic constipation 3, 4, 5, 6, 7
  • It has also been shown to improve health-related quality of life and patient satisfaction with treatment and bowel habit 3, 4, 5, 6, 7

Safety and Tolerability

  • Prucalopride has been generally well tolerated in clinical trials, with the most common adverse events being headache, nausea, abdominal pain, and diarrhea 3, 4, 5, 6, 7
  • No cardiovascular safety issues have been associated with prucalopride treatment 3, 4, 5, 6, 7

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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